MicroRNA-29a is involved lipid metabolism dysfunction and insulin resistance in C2C12 myotubes by targeting PPARδ

Abstract

MicroRNA-29a (miR-29a) expression has been reported to be closely associated with skeletal muscle insulin resistance and type 2 diabetes. The present study investigated the effect of miR-29a on palmitic acid (PA)-induced lipid metabolism dysfunction and insulin resistance in C2C12 myotubes via overexpressing or silencing of miR-29a expression. Mouse C2C12 myoblasts were cultured, differentiated and transfected with miR-29a or miR-29a inhibitor lentiviral with or without subsequent palmitic acid (PA) treatment. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to assess the mRNA and protein levels of related genes, respectively. PA treatment increased the expression of miR-29a in a timeand dose-dependent manner. miR-29a silencing improved insulin-induced glucose uptake and increased glucose transporter-4 (GLUT4) transportation to the plasma membrane by upregulating its target peroxisome proliferator-activated receptor δ (PPARd). Furthermore, it was observed that miR-29a regulated the expression of genes associated with lipid metabolism, including pyruvate dehydrogenase kinase isoform, mitochondrial uncoupling protein (UCP)2, UCP3, long chain specific acyl-CoA dehydrogenase, mitochondrial and fatty acid transport protein 2. The results confirmed that silencing miR-29a induced a decrease in glucose transport and affected lipid metabolism in PA-treated C2C12 cells, and therefore may be involved in insulin resistance by targeting PPARd in skeletal muscle. Therefore, the inhibition of miR-29a may be a potential novel strategy for treating insulin resistance and type 2 diabetes.